The severe anemia associated with hematologic disorders such as ? thalassemia, myelodysplastic syndrome, and congenital dyserythropoietic anemia, arises from defects in late stage erythroid maturation (dyserythropoiesis). In contrast to anemias resulting from early stage defects, this group of disorders are resistant to erythropoietin (EPO) therapy since late-stage erythroblast differentiation and maturation is EPO independent. Transfusion, often associated with iron overload and alloimmunization, remains the principal approach to care. Fortunately, however, several molecular determinants of dyserythropoiesis have been recently identified. It is possible that these discoveries may reveal common pathways leading to dyserythropoiesis